The invention relates to a pumping arrangement, for example for liquid, chromatography, wherein liquids from two or more reservoirs are delivered to an hydraulic resistance, such as a chromatographic separation column. Such a pumping arrangement can be used, for example, for gradient operation in preparative liquid chromatography.
High performance liquid chromatography (HPLC) is a well-known and widespread chromatographic technique to separate and analyze liquid samples containing different compounds of interest. The methodology of HPLC can be divided into two areas: analytical and preparative scale liquid chromatography.
The difference is reflected in the instrumentation setup, which typically consists of a liquid pump, an injection module, one or more chromatographic separation columns, at least one detection module, and in preparative liquid chromatography, always one or several fraction collection devices.
Analytical scale HPLC pumps are typically working in the flow rate range of 1-5 ml/min. They use active pump valves. In most cases the inlet or outlet valve has a spring support so that the liquid path in the pump head is actively closed at no flow conditions. Thus, in a gradient system consisting of multi channel pump modules, undesired mixing of different solvents will be prevented.
HPLC pumps working at flow rates above 10 ml/min up to several hundred ml/min do not have active pump valves.
In order to achieve precise gradients at high flow rates, various conditions with regard to liquid handling have to be fulfilled:
Three very important aspects, which are also addressed in the present invention, are as follows:
a) Filtration of liquids at high flow rates.
b) Handling of liquid flow when using high volume liquid containers at different storage levels in a laboratory.
c) Management of the liquid priming process.
With regard to the mentioned aspects a) to c), the prior art and the problems encountered are as follows:
a) Filtration of liquids at high flow rates is important in order to prevent access of fades or other small impurities that could enter into the pump head. They can prevent proper valve sealing, causing flow irregularities. Furthermore they may increase the system pressure over time, due to plugging of instrumental parts or the column inlet itself.
Most often inlet filters made out of sintered metal are used. Over time they are prone to become rusty or they may plug very soon because of their limited free surface area and thus their overall reduced capacity. In practice they are prone to error and have to be replaced very often. With bioanalytical applications, such as the separation of proteins, stainless steel filtration devices are not the matter of choice because of possible protein-metal interaction processes.
b) High flow HPLC pumps require plungers having much greater cross section than analytical pumps. As a matter of fact such plungers cause cavitations within the valves very easily and will destroy the ball seat as well as the ball itself in a very short period of time. In this case manual stop valves are used for interactive work to prevent undesired crossflow between liquid containers at different storage levels. For routine and automatic controlled systems electrically controlled stop valves are used. However, they are expensive and limited in lifetime.
c) Priming high flow HPLC instrumentation is of general importance. This can be done by cumbersome manual sucking the air volume out of the tubing with a syringe. This, however, is very inconvenient and time-consuming for the chromatographer.
It is thus an object of the invention to provide a pumping arrangement, which avoids the problems and disadvantages of the prior art.
Specifically, it is an object of the invention to provide a pumping arrangement with an improved filtering device having increased lifetime and filtering efficiency.
It is a further object to prevent uncontrolled cross flow in case that liquid reservoirs are stored at different height levels.
The pumping arrangement of the invention comprises:
a first liquid reservoir at a first height level, connected via a first hydraulic path to a pumping means;
a second liquid reservoir at a second height level, connected via a second hydraulic path to the pumping means; and
first and second filtration devices arranged in the first and second hydraulic path, respectively, wherein each filtration device comprises an outer member forming a first chamber, and an inner member arranged within the outer member and forming a second chamber, with the inner member being porous for allowing liquid flow from the first chamber to the second chamber.
The invention has the additional advantages that it is particularly suitable for handling non-degassed solvents and for the liquid priming process. One of the characteristics of the present invention is that the filtration device embodies several functions in one device, such as the filtering function and the prevention of undesired backflow.
According to a preferred embodiment of the invention the filtration devices are arranged at the same height level. In a further preferred embodiment, the first (outer) chamber of the filtration device accommodates a two-phase system comprising liquid from a liquid reservoir and vapor of this liquid.
It is another advantage of the invention that the filtration device can be reused after blockage by impurities, since it can easily be cleaned, for example with ultrasound cleaning. Furthermore the filtration device can easily be sterilized before use.